Method and apparatus of sterilization using monochromatic UV radiation source

ABSTRACT

This invention provides a process of sterilizing a medical device, and preferably the contents of a sealed container which comprises said medical device, comprising the step of exposing said medical device to monochromatic ultraviolet radiation whereby the D value  of  Bacillus stearothermophilus  (ATCC 7953) is at least 23.7 mJ/cm 2  monochromatic ultraviolet radiation at 257 nm to the spore. Further, this invention provides a process of sterilizing a medical device comprising the step of subjecting said medical device to monochromatic ultraviolet radiation wherein the minimum total energy density of said monochromatic ultraviolet radiation at 257 nm which reaches the microorganisms present on said medical device is at least 284 mJ/cm 2 . 
     This invention further provides an apparatus for delivering UV radiation to a medical device for sterilization comprising a laser and a scanner for the laser such that at least 284 mJ/cm 2  at 257 nm is applied to a treatment area for said medical device. This invention provides a process and apparatus in which sterilization can be achieved in less than 20 seconds, preferably less than 15 seconds, more preferably in less than 5 seconds. The process and apparatus are efficient and continuous.

This application is a continuation of “Method and Apparatus ofSterilization Using Monochromatic UV Radiation Source”, U.S. Ser. No.10/939,818, filed Sep. 13, 2004 now U.S. Pat. No. 7,879,288, which is acontinuation of U.S. Ser. No. 09/947,873, filed Sep. 6, 2001 nowabandoned, which is a continuation-in-part of a “Method OfSterilization”, U.S. Ser. No. 09/259,758, filed Mar. 1, 1999 nowabandoned.

FIELD OF THE INVENTION

This invention relates broadly to sterilization of medical devices. Morespecifically, this invention relates to a novel process and apparatusfor the sterilization of medical devices using monochromatic ultravioletradiation from one or more monochromatic UV radiation sources.

DESCRIPTION OF THE RELATED ART

Medical device sterilization processes, and in particular commercialcontact lens manufacturing sterilization processes, typically involvesome form of temperature and/or pressure-based sterilization techniques.For example, a hydrophilic contact lens is typically first formed byinjecting a monomer mixture into a mold. The monomer mixture is thenpolymerized (i.e. the lenses are cured). Afterother optional processingsteps, such as quality inspections, the lens is placed into a containerwith a solution and the container is sealed. The packaged lens issterilized by placing the container into an autoclave at an elevatedtemperature and pressure for an extended period of time, usually atleast 15 minutes, typically 30 minutes. Although this commercial processproduces thoroughly sterilized contact lenses, the batch-wise autoclavesterilization step is time consuming and costly.

European Patent Application No. 0 222 309 A1 discloses a process usingozone in which packaging material is disinfected in a manufacturingsetting. The process involves feeding an oxygen stream into an ozonatingchamber, generating ozone from oxygen in the ozonating chamber, placingpackaging containers in a sanitizing chamber, feeding the ozone into thesanitizing chamber, and purging the ozone from the sanitizing chamberwith sterile air. The process requires that the ozone contact thepackaging material for a predetermined time, followed by the sterile airpurge step. The process is offered as an alternative to heat-steamsterilization, sterilization by application of electromagneticradiation, or chemical agent sterilization.

U.S. Pat. No. 5,618,492 discloses a process for producing a sterilecontact lens in a sealed container during a continuous productionprocess wherein the contact lens is immersed in an ozone-containingsolution within a container during a continuous lens packaging process,and the lens and container are subsequently subjected to monochromaticultraviolet radiation primarily to degrade the ozone. This processsterilizes the contact lens and the container.

Non-ionizing radiation such as monochromatic ultraviolet (UV) light isknown to damage the DNA of exposed cells. The UV radiation causesthymine to dimerize which inhibits replication of DNA during cellreproduction. UV radiation is used for disinfection in hospital rooms,nurseries, operating rooms and cafeterias. UV radiation is also used tosterilize vaccines, serum, toxins, municipal waste, and drinking waters.The major weakness of the efficacy of UV radiation as a sterilizer isthat for most materials the radiation is not very penetrating, so themicroorganisms to be killed must be directly exposed to the radiation.

A number of patents teach the application of UV radiation to disinfectand/or inactivate microorganisms to either reduce populations ofmicroorganisms or to eliminate them.

U.S. Pat. No. 5,768,853 and WO96/09775 describe the use of a UVradiation producing apparatus which deactivates microorganisms in food.

U.S. Pat. No. 4,464,336 suggests a method of sterilization by using aflash discharge monochromatic ultraviolet lamp. The patent teaches thatby applying short duration high intensity UV radiation thatmicroorganisms will be destroyed; however, the conditions forsterilization are not disclosed, nor its application for medicaldevices.

U.S. Pat. No. 5,786,598 discloses the broad concept that a flash lampsystem might be used for deactivating microorganisms in containersincluding a polyolefin container with a foil backing that contains acontact lens and a preservative fluid. Preservation is the use ofphysical and/or chemical means to kill or prevent the growth of thosemicroorganisms which, by their growth and/or activities, may causebio-deterioration of a given material or product. P. Singleton and D.Sainsbury, 1988. Dictionary of Microbiology and Molecular Biology, JohnWiley & Sons, New York, N.Y., pp. 702-703. Although the patent disclosesthe idea of using a flash lamp system to sterilize contact lenses in apreserved solution in a container, there are no conditions defined toaccomplish sterility, nor examples which show that sterility can beaccomplished.

U.S. Pat. No. 5,034,235 and U.S. Pat. No. 4,871,559 disclose the use ofintermittent pulses of very intense, very short duration pulses of lightto inactivate microorganisms on the surface of food products, andsuggests that the method can be used for packages, medical devices, andfood products in packages.

A number of patents teach the use of lasers to sterilize and/orinactivate microorganisms to either reduce populations of microorganismsor to eliminate them.

U.S. Pat. No. 3,817,703 discloses the use of a high energy densitypulsed laser of unspecified wavelength to sterilize wine.

U.S. Pat. No. 5,232,367 discloses the use of a high power pulsed Nd:YAGlaser in dental applications to sterilize the bacteria in a tooth cavityand accessory canals.

U.S. Pat. No. 3,941,670 teaches the use of an infrared CW laser to alterthe biological activity of molecular species, including sterilization.

U.S. Pat. No. 3,955,921 and U.S. Pat. No. 4,042,325 discuss the use of apulsed laser to induce a plasma inside a container which sterilizes it.

A pulsed laser was used to inactivate Bacillus subtilis spores depositedon to planar aluminum and polyethylene packaging surfaces, K. Warriner,et al, “Inactivation of Bacillus subtilis spores on packaging surfacesby u.v. excimer laser irradiation,” Journal of Applied Microbiology2000, 88, 678-685.

There still remains a need for a time-efficient, continuous, effectivesterilization process for pharmaceutical, medical, and cosmetic productswhich can be used in an inline mode in the manufacture of theseproducts.

SUMMARY OF THE INVENTION

This invention provides a process of sterilizing a medical device, andpreferably the contents of a sealed container which comprises saidmedical device, comprising the step of exposing said medical device tomonochromatic ultraviolet radiation whereby the D_(value) of Bacillusstearothermophilus (ATCC 7953) is at least 23.7 milliJoule per squarecentimeter (mJ/cm²) for monochromatic ultraviolet radiation to thespore. Further, this invention provides a process of sterilizing amedical device comprising the step of subjecting said medical device tomonochromatic ultraviolet radiation wherein the minimum total energydensity of said monochromatic ultraviolet radiation which reaches themicroorganisms present on said medical device is at least 25 mJ/cm².

This invention further provides an apparatus for delivering UV radiationto a medical device for sterilization. In one embodiment, the apparatuscomprises at least one laser and preferably a scanner or set of opticssuch that the product can be exposed to the radiation. In an alternateembodiment the apparatus comprises the use of excimer lamps and suitableoptical devices to concentrate the output of the lamps at the medicaldevice.

The process and apparatus of the invention is used to provide sterilizedmedical devices. Further, this invention provides a process andapparatus in which sterilization can be achieved in less than 20seconds, preferably less than 10 seconds, more preferably in less than 1second. This invention provides a process and apparatus which sterilizesmedical devices and optionally sterilizes the contents of the containersholding the medical devices. Preferably the process and apparatus can beincorporated into a manufacturing line. The process and apparatus areefficient and continuous.

DESCRIPTION OF THE FIGURES

The invention will be described with reference to the following figures:

FIG. 1 illustrates one embodiment of an apparatus of this invention;

FIG. 2 illustrates a second embodiment of an apparatus of thisinvention;

FIG. 3 illustrates a third embodiment of an apparatus of this invention;and

FIG. 4 shows a graph used to determine the D_(value) of Bacillusstearothermophilus (ATCC 7953).

FIG. 5 shows a graph used to determine the D_(value) of Aspergillisniger (ATCC 16404).

DESCRIPTION OF THE INVENTION

The term “sterile” or “sterilization” as used herein means the conditionof an object, or an environment, which is free of all living cells, allviable spores (and other resistant and disseminative forms), and allviruses and subviral agents capable of replication. Sterility is assuredby a minimum sterility assurance level (SAL) of 10⁻³, preferably 10⁻⁶,more preferably 10⁻⁹, and most preferably 10⁻¹² when the container isinoculated with 10⁶ microorganisms. The minimum sterility assurancelevel is dependent on the type of medical device. For example, forsterilization of a single-use contact lens, the USFDA requires a minimumsterility assurance level of 10⁻⁶ in the number of microorganisms percontainer. A sterility assurance level of 10⁻⁶ is the probability ofhaving 1 non-sterile package out of one million packages.

The “D_(value)” is the amount of energy required to kill 90% of theorganisms present. For steam sterilization, the D_(value) is the timerequired at a given temperature to reduce the number of viable cells orspores of a given microorganism to 10% of the initial number, accordingto P. Singleton and D. Sainsbury in Dictionary of Microbiology andMolecular Biology, 1988, John Wiley & Sons, New York, N.Y., pg. 256.According to ANSI standards for gamma radiation, the D_(value) is theradiation dose required to kill 90% of the organisms of a homogeneousmicrobial population, which is defined by assuming that the death ofmicrobes follows first order kinetics. In the case of non-ionizingradiation, the D_(value) will be the non-ionizing radiation doserequired to kill 90% of the organisms of a homogeneous microbialpopulation, which is defined by assuming that the death of microbesfollows first order kinetics. The D_(value) is calculated using theStumbo-Murphy-Cochran Equation: D_(value)=U/(Log N₀−Log N_(u)), where N₀is the initial number of microorganisms in each replicate unit, N_(u) is1 n(n/r), where n is the total number of replicate units exposed to thesterilizing dose U, and r is the number of units exposed to dose U thattest negative for growth. Using the D_(value), the sterilizing dose canbe calculated. For sterilization of a medical device such as asingle-use contact lens, the requirement is for a sterility assurancelevel of 10⁻⁶. The total dose required to sterilize the producttherefore equals D_(value) (log N_(o)−log N_(u)).

The term “ultraviolet radiation” or “UV radiation” means radiationhaving a wavelength or wavelengths between from 160 to 400 nm. If arange is specified following the term “ultraviolet radiation” or “UVradiation”, a narrower range of radiation is meant within the 160 to 400nm range. Further, the range specified, unless otherwise stated, meansradiation having a wavelength or wavelengths within the range.

The term “monochromatic ultraviolet radiation” or “monochromatic UVradiation” means radiation having a wavelength or wavelengths betweenfrom 160 to 400 nm, and the majority of the radiation is concentratedwithin a bandwidth of 3 nm. Preferably the wavelength or wavelengths ofthe majority of the radiation represent more than 70%, more preferablymore than 90% of the total radiation of the monochromatic UV radiation.Preferably the majority of radiation is within a bandwidth of 2 nm, morepreferably within 1 nm. If the term “monochromatic UV radiation” isfollowed by a single wavelength within parenthesis, that wavelengthrepresents the majority wavelength of the radiation. If the termmonochromatic UV radiation is followed by a range within parenthesis,then the majority wavelength is within the specified range and/or thetotal range of radiation is within the range specified. The preferredmonochromatic UV radiation has the majority wavelength or wavelengthswithin about 220 to 320 nm, more preferably within 240 to 280 nm.Preferably the total monochromatic UV radiation is within the range from220 to 320 nm, more preferably within from 240 to 280 nm. A wavelengthor wavelengths within these ranges are the most preferred, because thosewavelengths are the most effective at rendering a microorganism sterile.The more preferred wavelength ranges comprise 257 nm, and presently, themost preferred range has the majority of radiation at 257 nm.

Examples of monochromatic UV radiation sources that producemonochromatic UV radiation include lasers and excimer lasers and excimerlamps. Lasers can be gas, ion, excimer, metal vapor, semi-conductor, andsolid state. The terms “laser”, “lamps” and “monochromatic UV radiationsource”, unless otherwise indicated, may be used interchangeably in thisapplication. The monochromatic UV radiation source can be pulsed, orcontinuous. A continuous monochromatic uv radiation source is either onethat continuously emits radiation or that pulses at a frequency greaterthan 15 Hz. The radiation geometry provided by the apparatus can be beamexpanded, line focused or spot scanned. The only requirement is thatevery surface of the medical device receives a sterilizing dose ofradiation. An expanded laser or excimer lamp which can treat the entiremedical device in a single exposure is preferred. The preferredmonochromatic uv radiation source is a continuous (CW) frequency doubledlaser. Preferably the monochromatic uv radiation source is collimatedand/or coherent.

Alternatively, the medical device may be scanned using a monochromaticUV radiation source. There are two preferred scanning methods. Firstly,the medical device may be scanned using a raster scan which uses spotfocused radiation, and the radiation source, the radiation and/or themedical device can be moved in at least the x and y directions.Preferably the radiation and/or the medical device are moved in the xand y directions. More preferably the radiation is moved in at least onedirection by mirrors. If the radiation is moved in one direction, e.g.the x direction, by mirrors the medical device can be moved in the otherdirection, e.g. the y direction, for example by a conveyor. Mostpreferably the radiation is moved in the x and y directions by mirrors.The radiation is preferably from at least one radiation source,preferably a continuous source. For the raster scan, the scanning in they direction is preferably 0.8 to 1.2 Hz, and the scanning in the xdirection is preferably at least 70 times faster than the scanning inthe y direction or visa-versa. This is to avoid artificial harmonics inthe exposure area, that is, lissajous curves. Preferably the scanfrequency in the x direction is 84 to 100 scans/second. For a rasterscan, it preferably scans between 20-200 scans/sec, more preferably 60scans/sec, and each scan preferably overlaps between 25 to 75 percent,more preferably approximately 50 percent, of the prior scan width. Thebeam width of the laser is typically 0.8 mm to 2.5 mm, more preferablyabout 1.4 mm.

Secondly, the medical device can be scanned by using line focusedradiation preferably having a radiation beam width which is wide enoughto cover the medical device in the x direction, and then the medicaldevice, the monochromatic UV radiation source, and/or the radiation canbe moved in the y direction until the entire medical device is treatedwith a sterilizing dose of radiation. Preferably, either the radiation,preferably by using mirrors, or the medical device, for example by aconveyor, is moved in the y direction. A line focus can be made by usinga cylindrical lens which focuses a column-shaped laser beam into a line;or an excimer lamp may be formed into a line source, or the radiationfrom an excimer lamp may be focused into a line by its reflector system,e.g. by a trough ellipse or other conical-shaped reflector.

To deliver the necessary dose of radiation, the medical device can betreated or exposed multiple times, in this embodiment in which themedical device is scanned by scanning it multiple times. Multiple scanscan be accomplished by scanning over the same area of the medical devicemultiple times or scanning over the entire medical device once and thenscanning over the entire medical device again and/or again. Depending onthe embodiment, the radiation, radiation source or medical device can bemoved to treat the medical device multiple times. Preferably, theradiation is moved using mirrors, and/or the medical device is movedinto and through the target area/volume of the monochromatic uvradiation source, and then back through the target area/volume, forexample by a movable conveyor. Alternatively other means to convey themedical device such as hooks, or pusher bars can be used to transportthe medical device into and/or through the target area/volume. Theconveyor means can be used to transport the medical device duringexposure or simply to transport the medical device to the targetarea/volume of the monochromatic UV radiation source, and away from themonochromatic uv radiation source after treatment.

Examples of monochromatic uv radiation sources include those thatproduce monochromatic UV radiation at the desired wavelength(s), orthose whose wavelength(s) are frequency doubled, tripled, quadrupled, orotherwise tuned (e.g. by using a doubling crystal (e.g. alpha or betabarium borate (BBO), lithium triborate (LBO), or cesium lithium borate(CLBO) or optical parametric oscillator (OPO)) to produce uv radiation.Examples of these sources include argon ion lasers, krypton ion lasers,metal vapor lasers, (such as copper vapor lasers), and solid statelasers, such as, neodymium yttrium aluminum garnet (Nd:YAG), neodymiumyttrium aluminum fluoride (Nd:YAF), neodymium yttrium aluminum phosphate(Nd:YAP), neodymium vanadate (Nd:YVO₄), neodymiom glass (Nd:Glass), andsolid state lasers. Other sources of monochromatic UV radiation includegas discharge tubes filled with gas mixtures in a laser or an excimerlamp which produce excimers in an electric discharge. Examples of gasmixtures which produce excimers include krypton and chlorine (KrCl),krypton and fluorine (KrF), xenon and iodine (XeI), chlorine (Cl₂),xenon and bromine (XeBr), bromine (Br₂), xenon and chlorine (XeCl),xenon and fluorine (XeF) argon and chlorine (ArCl), and argon andfluorine (ArF). These monochromatic uv radiation sources can be pulsedor continuous sources. These are only examples, other monochromatic UVradiation sources can be used in this invention.

Examples of useful commercially available monochromatic UV radiationsources include lasers available from Lambda Physik. One useful pulsedlaser is a Krypton-Floride (Kr—F) laser produced by Lambda Physik havingan output at 248 nm. Examples of commercially available excimer lampsinclude Xenon-Iodide (XeI) from Quark Physics which produces radiationat 253 nm, Krypton-Fluoride (KrF) from Quark Physics which producesradiation at 248 nm. Another useful laser is a solid state CoherentVerde diode laser at 532 nm, which can be frequency doubled to 266 nmusing mbd-266 resident enhancement cavity.

The monochromatic UV radiation source may be used in conjunction withother structural and optical elements to direct the radiation at thetarget. The excimer lamp is preferably used in conjunction with areflector or reflectors. Alternatively the excimer lamp can be used witha beam integrator lens. The laser can be used with a scanner, mirror,such as galvo mirrors and turning mirrors, beam expander, chopper, beamsplitter, diffuser, or focusing optics, such as lenses which focus thelaser radiation into a spot or a line, or combinations of the abovelist. The optics are used to provide the proper dose of radiation to thetarget. Further, a despeckler device such as a diffusing or oscillatingsurface may be used to remove or mitigate the intensity variations inthe radiation from the monochromatic UV radiation source on the micronscale due to interference speckle. In one embodiment, e.g. an apparatusof this invention comprises a laser in a scanning apparatus consistingof at least two mirrors which move a spot-focused beam back and forth inthe target area.

This invention can be used to sterilize medical devices. Theconfiguration of the system used to sterilize the medical device dependson the transmissivity of the medical device to monochromatic UVradiation. If the medical device is transmissive to at least a portionof the monochromatic ultraviolet radiation (preferably from 240 to 280nm), for example, preferably greater than 10%, more preferably more than50%, most preferably more than 75%, then a single monochromatic UVradiation source can be used to sterilize the medical device as long asat least 50 mJ/cm², more preferably at least 100 mJ/cm², most preferablyat least 200 mJ/cm² of UV radiation reaches all the microorganismsand/or all surfaces of the medical device to be sterilized. In addition,if the medical device is transmissive to at least a portion of themonochromatic ultraviolet radiation (preferably from 240 to 280 nm), forexample, preferably greater than 10%, more preferably more than 50%,most preferably more than 75%, then a single monochromatic continuous UVradiation source can be used to sterilize the medical device as long asat least 100 mW/cm², more preferably at least 250 mW/cm², mostpreferably at least 500 mW/cm² of UV radiation reaches all themicroorganisms and/or all surfaces of the medical device to besterilized. If the medical device is not transmissive to monochromaticUV radiation (preferably from 240 to 280 nm) or is transmissive to sucha small percentage of UV radiation, for example, less than 10%, thenmore than one monochromatic UV radiation source will most likely benecessary to sterilize the medical device, or the radiation produced bya single monochromatic UV radiation source will have to be split, e.g.by a beam splitter, and directed at the medical device from differentdirections. However, any configuration and any number of monochromaticUV radiation sources can be used as long as the minimum levels of energyspecified herein reach all the microorganisms or all the surfaces of themedical device which are to be sterilized.

Additionally, multiple monochromatic radiation sources, where at leastone is a monochromatic uv radiation source can be used together toaccomplish sterilization. Two or more monochromatic uv radiation sourcescan be used together to provide the same or different amounts of energyof the same wavelengths of monochromatic uv radiation to the medicaldevice, or they can provide the same or different amounts of energy atdifferent wavelengths of monochromatic uv radiation. The differentlevels of energy may be necessary to provide to the medical devicebecause of the shape or transparency of the medical device. Thedifferent wavelengths may provide increased levels of sterility, becausedifferent microorganisms that have to be sterilized on a medical devicemay have greater or lesser sensitivities to uv radiation at differentwavelengths; therefore, multiple monochromatic uv radiation sources canbe used which produce monochromatic uv radiation at differentwavelengths which when used together will successfully sterilize all themicroorganisms, that might not otherwise be sterilized, or would requiregreater levels of energy if only one monochromatic uv radiation sourceis used.

Alternatively, a monochromatic uv radiation source of this invention canbe used in combination with one or more monochromatic radiation sourceswithin the visible or infrared radiation spectra. Some microorganismshave an action spectrum with peaks outside the uv region. For thesemicroorganisms a combination of sources one of which is a source whichproduces radiation outside of the uv region and the other amonochromatic uv radiation source will provide sterilization. Forexample, vegetative microorganisms and sporolated fungi with dark sporecoats are more easily sterilized and at lower levels of radiation usingcombinations of monochromatic sources producing radiation within the uvand visible ranges, and uv and infrared ranges. Another benefit of usingmore than one monochromatic radiation source wherein at least one is amonochromatic uv radiation source at particularly effective wavelengthis that that same wavelength may cause damage to the package or themedical device and therefore cannot be used at the levels of energynecessary to achieve sterility; however, in combination with anothermonochromatic radiation source is effective to achieve sterility.

This invention is preferably used to sterilize medical devices which arein sealed containers. If the medical device is to be sterilized afterplacing it in its container, the container must be at least partiallytransmissive to at least a portion of the monochromatic ultravioletradiation (preferably at the majority of the radiation), preferably thecontainer is transmissive to at least 25% of the monochromaticultraviolet radiation (preferably at the majority of the radiation),more preferably the is container is transmissive to at least 50% of themonochromatic ultraviolet radiation (preferably at the majority of theradiation), and most preferably the container is transmissive to atleast 75% of the monochromatic ultraviolet radiation (preferably at themajority of the radiation). Ideally, the container is transmissive tosubstantially all of the monochromatic ultraviolet radiation. If themedical device is transmissive to at least a portion of themonochromatic ultraviolet radiation (preferably at the majority of theradiation), and a monochromatic UV radiation source is used to sterilizethe medical device, and if the medical device is in a container, thenthe container can be transmissive to at least a portion of UV radiationonly in one area of the container, as long as enough radiation can reachall the microorganisms and all of the surfaces of the medical device andcontents of the container. (The contents of the container include theinside surfaces of the container and any solution or other storagemedium for the medical device which is inside the container). However,if more than one monochromatic UV radiation source is used, it ispreferred that the container is at least partially transmissive tomonochromatic ultraviolet radiation at least at the majority of theradiation over most of the surface area of the container, and preferablysubstantially over the entire surface area, that is, that the container,at the time of exposure to the sterilizing radiation, preferably doesnot comprise any materials that have less than 10%, more preferably notless than 25% monochromatic ultraviolet radiation transmissivity at themajority of the radiation. More preferably, the container istransmissive in substantially all directions to at least 50% of themonochromatic UV radiation (preferably at the majority of theradiation), and most preferably the container is transmissive insubstantially all directions to at least 75% of the monochromatic UVradiation (preferably at the majority of the radiation). Ideally, thecontainer is transmissive in substantially all directions tosubstantially all of the monochromatic UV radiation.

Examples of medical devices which may be used in the process of thisinvention include, for example, catheters, surgical equipment, implants,stents, sutures, packing, staples, and bandages, and the like. Materialswhich may be used to make the medical devices include metals, glycerolmonomethythacrylate, polyvinyl alcohol, polyvinypyrrolidone,2-hydroxyethyl methacrylate (HEMA),methacryloxypropyltris(trimethylsiloxy)silane, polydimethylsiloxane,methylacrylic acid, methylmethacrylate, urethanes, polypropylene,polylactide, polyglactide, polyethylene glycol, polypropylene glycol,and the like, and the materials described below.

To decrease the complexity and energy demands of this method ofsterilization, it would follow that it would be preferred that themedical device is at least partially transmissive to monochromaticultraviolet radiation (preferably at the majority wavelength),preferably the medical device is transmissive to at least 10% of themonochromatic ultraviolet radiation (preferably at the majoritywavelength), more preferably the medical device is transmissive to atleast 25% of the monochromatic ultraviolet radiation (preferably at themajority wavelength), and most preferably the medical device istransmissive to at least 50% of the monochromatic ultraviolet radiation(preferably at the majority wavelength). The preferred medical devicetreated by the method of this invention is a contact lens. It is morepreferred that the contact lens is in a hermetically sealed contact lenscontainer, and even more preferred that the contact lens container holdsa liquid in which the contact lens is immersed. Even though the methodwould be simplified by using a UV transmissive medical device, thepresently preferred contact lens is a contact lens comprising aUV-blocker which blocks greater than 30%, more preferably greater than50%, and most preferably greater than 80% of the UV radiation (200-400nm) impinging upon it. The preferred embodiment, the process ofsterilizing a contact lens, will be described herein; however, it isapparent that other medical devices, such as those listed above, can besubstituted for the contact lenses in the method described in detailbelow for contact lenses.

It is preferred that the process of this invention is incorporated intoan in-line continuous contact lens manufacturing and packaging process.In the most preferred embodiment, the contact lens is formed and placedin a contact lens container, solution is added to the container, thecontainer is sealed and the container is subjected to short duration,high intensity radiation from a monochromatic UV radiation source,preferably a laser producing a majority of the radiation at 257 nm,either by scanning or pulsing, to produce a sterile packaged contactlens which is ready for distribution and use. In the preferredembodiment, the contact lens comprises a hydrogel material and thecontact lens is stored in an aqueous solution in the container. Themanufacture and placement of the contact lens in the container can be byany process for making contact lenses including those described in, forexample, U.S. Pat. Nos. 5,435,943; 5,395,558; 5,039,459; 4,889,664;4,565,348; 4,495,313, incorporated herein by reference. Other methods ofmanufacturing contact lenses are disclosed in other patents, and areknown to a person of ordinary skill in the art.

The preferred method provides that a contact lens mold is formed byinjection molding two thermoplastic contact lens mold halves which, whenput together, form a cavity in the shape of the contact lens. Thesethermoplastic contact lens molds are typically used once to form acontact lens. Reusable lens molds made out of more durable materials,for example, glass or metal can also be used. Typically, before the lensmolds are put together, the monomer or prepolymer mixture which formsthe contact lens polymer is injected into a first mold half and a secondmold half is placed onto the first mold half which pushes out any excessmonomer or prepolymer mixture. However, a one-piece mold can be used toform the contact lens, or the monomer or prepolymer mixture can beinjected between the molds after assembly of the molds. The monomer orprepolymer mixture is then cured to form the contact lens. Curing of themonomer or prepolymer mixture is preferably initiated by usingphotoinitiation. After curing the monomer or prepolymer mixture, themold halves are removed, and the contact lens is hydrated, if needed.After hydration, preferably one contact lens is placed in a contact lenscontainer. It is preferred that each contact lens container alsocontains at least enough aqueous solution to fully wet the contact lensin the container, but the presence of aqueous solution is not requiredin the process of this invention. The aqueous solution, if present, canbe added to the container before or after placing the contact lens inthe container. Further, the container can be sealed before or after thesterilization step. Alternatively, the container can be sealed beforeand after the sterilization step if multiple layers of the container areadded in multiple steps. For example, a sealed container can beshrink-wrapped or a label added after the sterilization step; or therecan be multiple sterilization steps before and after sealing thecontainer. For example, the container can undergo the sterilization stepwhile empty, and/or when it has liquid in it and/or when it has acontact lens placed in it and is not sealed, and/or after the containeris sealed with the contact lens and optional liquid present in thecontainer. In additional embodiments, the individual parts and contentsof the container can be individually treated by the method of thisinvention, and then assembled, and/or treated again. It is presentlypreferred to hermetically seal the container in which a contact lens ispresent prior to the process of sterilization, and to perform the stepof subjecting the hermetically sealed container having the contact lenstherein to UV radiation (preferably 257 nm) only once. The container canbe sealed by any means which provides a hermetically sealed container.

The contact lenses useful in accordance with the present invention maybe formed from any materials useful for contact lenses. For example, thelenses may be hydrophilic lenses formed from the polymerization orcopolymerization of acrylates or methacrylates, such as 2-hydroxyethylmethacrylate (i.e., HEMA); hydrophobic lenses formed from polysiloxanes;or lenses formed from copolymers displaying a range of hydrophobic andhydrophilic properties. The preferred contact lens material isEtafilcon-A which comprises HEMA, MAA, EGDMA, TGDMA, and Darocur. Usefulcontact lens materials are described in U.S. Pat. Nos. 5,484,863;5,039,459; 4,889,664; 5,0684,058; 5,654,350; 5,648,402; 5,311,223;5,304,584; 5,256,751; 5,196,458; 4,495,313; and 4,680,336, incorporatedherein by reference.

Additionally, the process of this invention can be used to sterilizecontact lenses which contain ultraviolet radiation blocking agents.Contact lenses containing monochromatic ultraviolet radiation blockingagents include, Acuvue® and Surevue® made by Johnson & Johnson VisionProducts. Blocking agents which can be used in contact lens compositionsinclude Norbloc™ 7966, which is2-(2′-hydroxy-5-methacryloxyethylphenyl)-2H-benzotriazole; otherbenzotriazoles, such as,2-(2′-hydroxy-5′methacrylyloxyethylphenyl)-2H-benzotriazole;2-{3′-tert-butyl-2′-hydroxy-5′-(3″methacryloyloxypropyl)phenyl}-5-chlorobenzotriazole;and benzophenones, such as,1,3-bis(4-benzoyl-3-hydroxyphenoxy)-2-propyl)(meth)acrylate;2-hydroxy-4-((meth)acryloxyethoxy)benzophenone;4-methacryloxy-2-hydroxybenzophenone, others disclosed in U.S. Pat. Nos.5,133,745; 4,528,311; 4,716,234; 4,528,311 and 5,681,871, and othersknown to a person of ordinary skill in the art. Contact lenses can bemade according to the examples and teachings in U.S. Pat. Nos.5,133,745; 4,716,234; 4,528,311; 4,304,895 and 5,681,871. Also theprocess of this invention can be used to sterilize contact lenses whichcontain tints, including visibility tints, including Reactive Blue #4(2-anthracenesulfonic acid,1-amino-4-(3-((4,6-dichloro-s-triazin-2-yl)amino)-4-sulfoanilino)9,10-dihydro-9,10-dioxo-)and other materials disclosed in U.S. Pat. No. 5,292,350. The mostpreferred lens material is Etafilcon-A further comprising Norbloc™ andReactive Blue #4.

The aqueous solution, if present in the contact lens container, ispreferably buffered to a pH of between about 6.5 to about 7.8 in orderto approximate the pH of the fluids in the eye. The solution may bebuffered by a wide variety of buffers including phosphates, borates,citrates, and other biocompatible buffers known to a person of ordinaryskill in the art. The presently preferred buffer is a borate solution.The amount of solution depends on the size of the container. Thesolution preferably does not contain any preservatives. Typically, thecontainer has a volume between 0.5 milliliters and 50 milliliters,preferably about 1 milliliter, and there is between 0.1 milliliter to 1milliliters, preferably about 0.5 milliliters of solution in thecontainer.

Containers which are useful in this invention are any of the knowncontainers which are or can be hermetically sealed as long as thecontainers are at least partially transmissive to monochromaticultraviolet radiation (preferably from 240 to 280 nm). The containerscan be UV transmissive glass, thermoplastic pouches and bags, cyclicolefin copolymers, injection molded or thermoformed plastic containers,and conventional bowls and lids for contact lenses, as long as enoughmonochromatic ultraviolet radiation (preferably from 240 to 280 nm) canpenetrate the container to sterilize the contents of the container. Itis presently preferred that the contact lens container comprises a bowland a lid. It is preferred that the material or materials of at leastthe bowl of the container are at least partially transmissive tomonochromatic ultraviolet radiation. Particularly, for the sterilizationof a contact lens comprising UV-blocker, it is even more preferred thatthe bowl and the lid are at least partially transmissive tomonochromatic ultraviolet radiation, preferably in all directions. Toaccomplish this, it is preferred to replace the conventional foil lidwith a thermoplastic lid, which may consist of one or more layers of,for example, Aclar, nylon, polyamide, polyvinylidenefluorides (PVDF),polyvinylchlorides (PVC), Saran (polyvinylidene chloride (PVDC)), Sarancoated PVC, polyfluorides, e.g. polytetrafluorethylene, castpolypropylene, acrylics, polyethylenes, polystyrenes, andpolychlorofluorides e.g. polychlorotrifluoroethylene, polyesters, andcopolymers of these materials and cyclic olefin copolymers. It ispresently preferred that the bowl is a polyolefin, and the lid comprisespolypropylene. The materials of the bowl and the lidstock shouldpreferably be free of any component that will scatter light. The mostpreferred method of sealing the container is to heat seal thethermoplastic lid to the thermoplastic bowl. The most preferredcontainers and materials for the container are described in James Peck,et al, U.S. Ser. No. 09/259,795, titled, “Package for Medical Device”(VTN-445) filed Mar. 1, 1999 which is incorporated herein by reference.

Sterilization of the contact lens and preferably the contents of thecontainer is achieved by subjecting the container to high intensityradiation, preferably in a short duration, comprising monochromaticultraviolet radiation (preferably from 240 to 280 nm) from amonochromatic UV radiation source, wherein the energy density of saidhigh intensity monochromatic ultraviolet radiation (preferably from 240to 280 nm) inside said container is sufficient to provide completeinactivation of the respective microorganisms. The radiation preferablycomprises UV radiation in the range 240-320 nm, because it has beendetermined that radiation at these wavelengths is most responsible forthe inactivation of microorganisms. Different microorganisms are knownto be affected differently by monochromatic ultraviolet radiation (atthe specific individual wavelengths between about 240 and 280 nm).Viruses are susceptible to UV radiation, and vegetative bacteria aremore susceptible to UV radiation. The spore-forming microorganisms areknown to be the most resistant to UV radiation. The reasons for theresistance of the spores to UV radiation is primarily attributed to thecomposition of the outer coat of the spore and the ability of spores torefract light. We have determined that one of the most resistantmicroorganism to this method of sterilization is Bacillusstearothermophilus (ATCC 7953). The D_(value) for Bacillusstearothermophilus (ATCC 7953) is at least 23.7 mJ/cm² monochromaticultraviolet radiation (257 nm) to the spores. The Dvalue was determinedusing an apparatus having a continuous, scanning frequency doubled Arion laser producing radiation at 257 nm (2 W) Coherent Innova® Sabre®,FreD™, which will be described in greater detail below. For a sterilityassurance level of 10⁻³, using the Dvalue 23.7 mJ/cm², the dose to themicroorganisms (where the initial inoculum is 10⁴ cfu/container) is atleast 166 mJ/cm² of UV radiation (257 nm). For a sterility assurancelevel of 10⁻⁶, the dose to the microorganisms is at least 237 mJ/cm² ofUV radiation (257 nm). For a sterility assurance level of 10⁻⁹, the doseto the microorganisms is at least 308 mJ/cm² of UV radiation (257 nm).For a sterility assurance level of 10⁻¹², the dose to the microorganismsis at least 379 mJ/cm² of UV radiation (257 nm). For an initial inoculumof 10⁶, the microorganisms are exposed to at least 284 mJ/cm² of said UVradiation (257 nm) to provide a sterility assurance level of 10⁻⁶. Inthe preferred embodiment, in which the medical device is a UV-blockerlens in a container having approximately 50% transmissivity for UVradiation (257 nm), the energy is provided by two lasers each of whichprovides at least 284 mJ/cm² UV radiation (257 nm) to the container, andthe lasers irradiate both sides simultaneously, whereby the contactlens, and more preferably the contact lens and the contents of thecontainer are rendered sterile. The container permits approximately 50%of the UV radiation impinging on it from each laser to reach thecontents of the container. The amounts of energy, and D_(values)required for sterility may vary depending upon the wavelength(s)provided by the monochromatic uv radiation source(s), and the deliverymechanism of the radiation, and the medical device to be sterilized.

As described above, the high intensity monochromatic ultravioletradiation can be generated and directed to the container by one or moremonochromatic UV radiation sources, e.g. lasers or excimer lasers orlamps, with or without reflectors, lightguides, lightpipes, fiberoptics, dioptric or catadioptric optical systems to focus light on theproduct. It is preferred that at least 75% or more of the total energywhich reaches all the surfaces of the medical device to be sterilized isultraviolet radiation (preferably from 240 to 280 nm). For a medicaldevice in a container, it is preferred that at least 75% or more of thetotal energy which reaches all the surfaces of the medical device, andthe contents of the container is UV radiation (preferably from 240 to280 nm). For many polymers which are commonly used for contact lenscontainers and contact lenses, which were described earlier, radiationat wavelengths less than 240 nm is absorbed by the polymers and maycause chain scissions within the polymers. Since the laser emits at asingle wavelength or a narrow range of wavelengths, a source whichproduces radiation below 240 nm can be avoided which is a benefit overbroad band radiation sources.

Sterilization of the container, which preferably comprises at least onecontact lens and aqueous solution is preferably achieved by subjectingthe contact lens and container to short duration, high intensitymonochromatic ultraviolet radiation, wherein the energy density of saidhigh intensity monochromatic ultraviolet radiation 257 nm at all thesurfaces of the contact lens is at least 166 mJ/cm², more preferably atleast 237 mJ/cm², most preferably at least 284 mJ/cm², whereby thecontact lens, and more preferably the contact lens and the contents ofthe container are rendered sterile.

In the preferred embodiment, the monochromatic ultraviolet radiation isdelivered to the medical device by a laser system which exposes theentire medical device simultaneously or scans the medical device. Themedical device can be scanned via a line laser or raster scan with anarrow spectrum of radiation (e.g. 257 nm). The exposures or scans areshort and intense, that is, the exposures or scans last less than 5seconds, more preferably less than 3 seconds, and most preferably lessthan 1 second. In the preferred system each exposure of the entiremedical device lasts less than 0.5 second, more preferably less than 0.1second, most preferably about 1 millisecond, and the time betweenexposures of the medical device, if more than one exposure is necessaryto achieve sterility is about 100 to about 200 milliseconds; therefore,the sterilization process can be completed within a few seconds even ifit takes multiple exposures to deliver the sterilizing dose. The pulsesor exposures deliver enough energy to sterilize the medical device andcontents of the container. Each exposure of energy in this systemdelivers a large amount of energy to surfaces of the contact lens andthe container in a short period of time. It is preferred that at least284 mJ/cm² (257 nm) reaches the surface of the contact lens in less than10 milliseconds, more preferably in less than 1 millisecond, mostpreferably in less than 500 microseconds. More preferably, at least 1J/cm² reaches the microorganisms in less than 1 millisecond. It has beenfound that the effectiveness of the system at sterilizing is dependentnot only on the total amount of energy that is supplied to thecontainer, but that there is a maximum amount of time (and exposures) inwhich that energy needs to be delivered to the container. It has beendetermined that the energy required to render the contact lens sterileis preferably delivered to the surface of the contact lens in at mostthree exposures, more preferably at most two exposures and mostpreferably in one exposure of radiation from at least one source in apulsed or scanning UV radiation system. It is preferred that themonochromatic uv radiation source in the preferred embodiment providesat least 284 mJ/cm², more preferably at least 568 mJ/cm², and mostpreferably at least 1.2 J/cm² UV radiation (257 nm) in each exposure tothe microorganisms. It is also preferred that the laser in the preferredembodiment produces at least 568 mJ/cm², more preferably at least 1.2J/cm² and most preferably at least 2.4 J/cm² UV radiation (257 nm). Itis preferably with a minimum of 568 mJ/cm² delivered in each exposure.For a medical device in a container, the medical device having less than20% transmissivity (257 nm), it is preferred that multiple monochromaticuv radiation sources are used simultaneously to produce at least 900mJ/cm² total UV radiation (257 nm) per exposure, more preferably atleast 1.2 J/cm² total UV radiation (257 nm) per exposure, and mostpreferably at least 2.4 J/cm² total UV radiation (257 nm) per exposureof the container.

The application of the short duration, high intensity monochromaticultraviolet radiation can be accomplished by using one or more lasers.In the preferred embodiment, if one laser is used it is preferablydirected at the contact lens at the base, preferably the bowl, of thecontainer. If two sources of radiation are used, or the radiation from asingle source is split into two, preferably one is directed at thecontact lens through the base and the other is directed at the top,preferably through the lid of the container. As long as the contents ofthe container receives a sterilizing dose of radiation, and each singlecell of microorganism is exposed to sufficient energy to inactivate it,the configuration of the sources of the radiation is not important. Onlyone laser is necessary when the container and medical device havesufficient transmissivity to allow sufficient energy to transmit throughthe container and device to affect sterility on the entire contents ofthe container. For example, one laser may be effective for a containerholding a contact lens which does not have a UV-blocker in its polymer,or a contact lens that is transmissive to greater than 30%, morepreferably greater than 50% of UV radiation (257 nm).

The presently preferred apparatus for delivering the high intensityradiation to the contact lens having a UV-blocker in a container with anaqueous solution in the container is a frequency-doubled Argon ioncontinuous wave (CW) laser from Coherent Laser (Santa Clara Calif.)which emits greater than 1 watt at 257 nm, and is capable of delivering150 mJ/cm² to the outside of the container. The preferred system isshown in FIG. 1. FIG. 1 shows two laser assemblies 21 and 31. Laserassembly 21 comprises laser 22, frequency doubler 23, turning mirrors 24and 25, scanner 26 comprising mirrors 27 and 28. Laser assembly 31comprises laser 32, frequency doubler 33, turning mirrors 34 and 35,scanner 36 having two mirrors 37 and 38. Also shown in FIG. 1 is thechamber 40. The chamber comprises a motion-controlled stage 47 to movethe product within and through the treatment area on the product support49. The laser assemblies 21 and 31 face each other with a space betweenthem for the product support 49 holding the container or containers tobe sterilized. The system is shown with one container 50 on the productsupport 49 ready for sterilization. The laser assemblies 21 and 31 scanthe container 50 simultaneously. Lines A and B show the radiation's pathto the container 50. Each laser assembly 21 and 31 generates a minimumof 284 mJ/cm² of UV radiation (257 nm), more preferably a minimum of 568mJ/cm² (257 nm) per exposure. The chamber 40 is preferably light-tightwhen the product is scanned, and more preferably the chamber 40 andlaser assemblies 21 and 31 are configured such that all are light-tight,and the junctions 51 and 52 between them allow the radiation A and B topass to the container 50, but not outside of the chamber 40 orassemblies 21 and 31. The container 40, comprises a contact lens andaqueous solution (not shown). Preferably, only when a light-tightchamber is established will the shutter on the laser be opened. It isbelieved that a light-tight chamber will prevent any photo-annealing ofthe microorganisms' damaged DNA after subjecting the medical device toUV radiation (preferably from 240 to 280 nm).

The containers are preferably placed between the two lasers so that thecontact lenses are closest to the center-line between the radiation fromthe two lasers. The product support 29 can consist of any materialswhich will hold the containers and permit enough monochromaticultraviolet radiation (257 nm) to reach the contents of the one or morecontainers. For example, it can comprise polymeric or other glassmaterials in any configuration which holds the containers, e.g. sheetmesh, or bars. It is presently preferred that the product supportcomprises quartz.

FIG. 2 illustrates a second embodiment of the invention which shows atreatment chamber 60 which comprises laser 61, frequency doubler 63,galvo mirror 67, spherical lens 68, and product support 69. The laserradiation beam 62 is shown exiting the laser, deflected by the galvomirror 67 and focused by spherical lens 68 onto a container 70 shown inthe product support 69. The galvo mirror 67 is used to raster scan thecontainer 70 in both the x and y directions. The spherical lens 68focuses the beam width down to a smaller point which increases theintensity of the radiation at that point.

FIG. 3 illustrates a third embodiment of this invention, which shows atreatment chamber 80 which comprises laser 81, frequency doubler 83,galvo mirror 87, cylindrical lens 88, and product support 89. The laserradiation beam 82 is shown exiting the laser, deflected by the galvomirror 87 and focused by cylindrical lens 88 onto a container 90 shownin the product support 89. The cylindrical lens 88 focuses the radiationbeam D into a line in the x-direction having a width (or length) greaterthan the container 90. The galvo mirror 87 is used to scan the container90 with the line of radiation in the y-direction.

The energy levels specified herein can be used to determine the exposurethat is required to sterilize a medical device in a container. Thetransmissivity of a container and the medical device within thecontainer must be determined. As taught herein, it is now known that theminimum level of energy which must reach the inside of the container andthe surface of the medical device to obtain sterilization must beequivalent to at least 450 mJ/cm² of UV radiation at 257 nm. Thefollowing formula can be used to calculate the amount of energy thatmust be provided from the one or more monochromatic uv radiation sourcesto achieve sterility. The following formula is suited for a system whichhas two monochromatic uv radiation sources, but can be modified if oneor more than two monochromatic uv radiation sources are used:

Total energy from all monochromatic uv radiation sources E=E_(a)+E_(b),where E_(a) is the energy above the contact lens in the container, andE_(b) is the energy below the contact lens in the container.where E _(a) =E _(U) [e ^(−k) _(LS) ^(x) _(LS) ]+E _(L) [e ^(−k) _(B)^(x) _(B) ][e ^(−k) _(L) ^(x) _(L)],and E _(b) =E _(U) [e ^(−k) _(LS) ^(x) _(LS) ][e ^(−k) _(L) ^(x) _(L)]+E _(L) [e ^(−k) _(B) ^(x) _(B)]where transmissivity T=I (intensity which penetrates a material)/I₀(intensity incident on a material)=e^(−kx) where k is the transmissivityconstant of a material at 257 nm and x is the thickness of the material.E_(U) is the energy from a monochromatic uv radiation source locatedabove the container. E_(L) is the energy from a monochromatic uvradiation source located below the container. The subscript LS indicateslidstock. The subscript L indicates lens. The subscript B indicatesbowl. E_(a) and E_(b) each have to be at least 3.6 J/cm² UV radiation(257 nm) to achieve sterilization of the medical device at an SAL of10⁻¹². If the transmissivity of the container or medical device isincreased or decreased, the energy of the lasers can be calculated,because E_(a) and E_(b) are known. (For the preferred embodiment herein,the contribution of the UV radiation (257 nm) which passes through theUV-blocking contact lens was assumed to be zero when determining theamount of UV radiation which the microorganism is subjected to on eachside of the lens.)

Initially, a prototype system consisting of one laser using mirrors toraster scan the package, like the one shown in FIG. 2, was evaluated forsterilization. The laser was capable of delivering 150 mJ/cm² to theoutside of the container. The laser was a frequency-doubled Argon ioncontinuous wave (CW) laser from Coherent Laser (CA) which emitted 1 wattat 257 nm. The system had a spherical mirror which focused the beam. Thebeam had an area of 0.7 m². The raster scan in the x direction was 90 Hzfor 23 mm and the y direction was 1 Hz for 23 mm which covered theportion of the contact lens container where the contact lens and thesolution was stored. The overlap area in consecutive scans was 0.35 mm.

Microbiological evaluation of the effectiveness of the system wasconducted using containers, consisting of bowls and lidstock, (bothabout 50% transmissible to UV radiation (257 nm)), holding UV-blockingcontact lenses (20% transmissive to 257 nm) in a non-preserved solutionof buffered borate. The test microorganism was added at a concentrationof 10⁴ colony forming unit/package (cfu/pkg). The closed intactcontainers were exposed to the laser and subjected to 100 mJ/cm² (257nm) from the laser. One hundred containers containing Bacillusstearothermophilus (ATCC 7953) or Aspergillus niger (ATCC 16404) sporeswere each exposed to a total of 100 mJ/cm² UV radiation (257 nm). Thecontainers inoculated with Bacillus stearothermophilus (ATCC 7953) werethen processed in a laminar flow hood whereby the entire contents of thecontainer were placed into potato dextrose broth and incubated at 25° C.for 14 days. The containers inoculated with Aspergillus niger (ATCC16404) spore preparations were transferred to tubes containing 40 ml oftrypticase soy broth and incubated for 14-days at 35-37° C. This tubeterminal sterilization method allows for the detection of the viabilityof 1-single cell. After 14-days of incubation, the tubes were visuallyevaluated for turbidity and designated as positive for growth ornegative for no growth. The positive tubes were subsequently identifiedand confirmed as the microorganism inoculated in the test. Thisexperiment was repeated with 100 additional tubes for 150 mJ/cm²exposure at 257 nm, and repeated again for 450 mJ/cm² cumulativeexposure at 257 nm. The number of test tubes with viable testmicroorganisms out of the one hundred tested at each energy level wererecorded in Table 1.

The results in Table 1 clearly show that the amount of energy producedby the system was capable of inactivating some of the testmicroorganisms; however, it was not effective in inactivating any of themore resistant spore formers. However, this system could be used todeliver enough energy in one exposure to sterilize a non-UV-blockingcontact lens in an aqueous solution in a container having transmissivitygreater than 50% for 257 nm radiation.

TABLE 1 Number of positive tubes/100 Microorganism 100 mJ/cm² 150 mj/cm²450 mj/cm² Bacillus 31 25 9 stearothermophilus (ATCC 7953) Aspergillusniger 100 100 100 (ATCC 16404)

Terminal sterilization was not achieved for Aspergillus niger for thisset of conditions. The Dvalue for Aspergillus niger was determined fromplate counts as follows:

6 random samples of each organism and condition were plated andprocessed as described below. Samples were serially diluted intoduplicate pour plates using standard plate count method were preparedfrom each dilution to a level of countable plates between 20-300 cfu.Bacillus stearothermophilus was diluted serially and added to petridishes followed by pouring tempered Trypticase Soy Agar. The agar wasallowed to solidify and then the plates were inverted and incubated at55-60 degrees C. for a maximum of 3 days. Aspergillus niger was seriallydiluted and added to petri dishes followed by pouring tempered PotatoDextrose Agar. The agar was allowed to solidify and then the plates ofAspergillus niger were inverted and incubated at 25-30 degrees C. for amaximum of 3 days.

After incubation, each plate was enumerated and the total counts for thetotal number of bacteria remaining in each package were determined.

100 package samples of each organism were exposed to each of theconditions outlined above. These samples were processed by placing thetreated contents of the blister package into 40 ml volumes of TrypticaseSoy Broth (B. stearo.) or Potato Dextrose Broth (A. niger) andincubating at stated temperatures for a period of 14 days.

Initial concentrations of each organism were:

B. stearo.=1.02×10⁶ spores/blister

A. niger=5.20×10⁵ spores/blister

The number of survivors for each microorganism for each of the treatmentconditions for the plate counts method are shown in Table 2.

TABLE 2 Number of colony forming units for each treatment. Bacillus Dosestearothermophilus Aspergillus niger (mj/cm²) Scans (ATCC 7953) (ATCC16404) 0 0 258000 53333 50 1 3 2858 100 1 1 842 100 3 0 2475 150 1 0 933150 3 0 2225 450 3 0 850

Dvalues were determine from the slope of the log of survivors andtreatment dose. The Dvalue is the energy required for a one logreduction. These data are shown in FIG. 4 and FIG. 5.

Although not preferred modes of this invention, it has been determinedthat this method of sterilization can be enhanced by adding chemicals,bactericides, surfactants, preservatives or heat to the contents of thecontainer. Also the method of sterilization can be enhanced by shakingthe container, or exposing the container to sonic vibration energy as itis exposed or between exposures to the laser or by heating thecontainer. These additional methods may be required to decrease theDvalue of Aspergillus niger which from the data above was at least 188mJ/cm².

This invention has been described with reference to particularembodiments; however, variations within the scope of the followingclaims are apparent to those of ordinary skill in the art.

1. A process of sterilizing a contact lens immersed in an aqueous liquidagainst Bacillus stearotheromophilus (ATCC 7953) to a sterilityassurance level of at least 10⁻⁶, wherein said contact lens and saidaqueous liquid are hermetically sealed in a container consisting of thestep of penetrating said hermetically sealed container containing acontact lens immersed in an aqueous liquid with at least 284 mJ/cm² inthe range of 240-280 nm of UV radiation from a monochromatic UVradiation source.
 2. The process of claim 1 wherein, said contact lensis exposed to at least 308 mJ/cm² of said UV radiation of 257 nm duringsaid penetrating step.
 3. The process of claim 1 wherein saidmonochromatic UV radiation source is at least one laser.
 4. The processof claim 1 wherein said penetrating step is accomplished by aline-focused laser scanning said hermetically sealed container.
 5. Theprocess of claim 1 wherein said penetrating step is accomplished bypulsing said hermetically sealed container.
 6. The process of claim 1wherein said monochromatic UV radiation source further comprises atleast one of the following group: reflector, beam integrator lens,scanner, mirror, beam expander, chopper, beam splitter, diffuser,focusing optics, and a despeckler.
 7. The process of claim 1 whereinsaid contact lens is transmissive to at least 25% of the monochromaticUV radiation.
 8. The process of claim 1, wherein said radiation isdelivered by more than 1 monochromatic UV radiation sourcessimultaneously.
 9. The process of claim 1, wherein said radiation isdelivered by more than 1 monochromatic UV radiation sources, saidmonochromatic UV radiation source producing differing wavelengths. 10.The process of claim 1, wherein said container is transmissive to atleast 50% of said monochromatic ultraviolet radiation at 257 nm.
 11. Theprocess of claim 1, further wherein said container is transmissive to atleast 50% of said radiation at 257 nm in substantially all directions.12. The process of claim 1 wherein said container comprises a lid and abowl, wherein said lid and said bowl comprise thermoplastics and saidlid and said bowl are transmissive to at least 50% of said radiation at257 nm in substantially all directions.
 13. The process of claim 1wherein said medical device is a contact lens, and wherein saidsubjecting step follows the steps of: (a) forming a contact lens; (b)placing said contact lens in a container; and (c) moving said containerinto an apparatus comprising a radiation source; and wherein saidapparatus is light-tight during said subjecting step.
 14. The process ofclaim 1 wherein said medical device comprises a contact lens comprisingUV-blocker which blocks greater than 50% of the radiation between 257nm.
 15. The method of claim 1 wherein the process is performed as a stepof an in-line continuous contact lens manufacturing and packagingprocess.